5-Fluorouracil derivatives. X. Synthesis and antitumor activities of .ALPHA.-alkoxyalkyl-5-fluorouracils.

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Abstract
With the aim of diminishing the toxicity of 5-fluorouracil (1) and obtaining biologically active derivatives of 1 suitable for oral administration, .alpha.-alkoxyalkyl groups were introduced the 1-, 3- and 1,3-positions of 1. Alkoxyalkylation can be effected by four methods: (i) reaction of 1-alkoxyalkyl chloride (2) with 1, (ii) reaction of acetal with 2,4-bis(trimethylsiloxy)-5-fluoropyrimidine, (iii) addition reaction of .alpha.-unsaturated ether with (1), (iv) aminolysis of 1-alkylthiocarbonyl-3-(1-alkoxyalkyl)-5-fluorouracil. The toxicity of the products was less than that of 1, and some of these compounds showed moderate antitumor activity against L-1210 leukemia.